Oregon is one of a few states where methamphetamine (MA) abusers without a greater history of cocaine abuse are recruited for clinical research. This renewal of the Methamphetamine Abuse Research Center (MARC) will characterize effects of MA at molecular, genetic, neurochemical, anatomical, behavioral, and clinical levels, to identify risks and obstacles to recovery in MA abusers. Integrated preclinical and clinical research components use some common methodologies and address MA-related themes of neuroadaptation, neurocircuitry, and neuroimmune effects. This renewal continues to pursue bidirectional translational research in which human and animal results inform one another. The Center's Administrative Core 1 supervises budgetary issues and facilitates interactions among MARC investigators, and the Biostatistics and Genetics Core 2 provides statistical and genetic analysis services. The Animal Core 3 provides genetic animal models and some behavioral testing services to MARC investigators. The Education Core 4 coordinates the research training of M.D. and Ph.D. pre- and post-doctoral fellows, and disseminates clinical and preclinical information from MARC investigators to other Centers and more rural areas that are impacted by MA abuse. The Translational Service Core 5 recruits and characterizes subjects and conducts identical biochemical assays on human and MA drinking selected mouse line samples. The Pilot Projects Core 6 supports the development of multiple new directions in research on MA abuse. Scientific Component 7 associates image analysis results with impulsive decision making in human and animal subjects. Scientific Component 8 examines the role of immune function in human cognitive response and tests a novel immunotherapy in mice, and Scientific Component 9 uses MA drinking selected mouse lines to examine the role of immune function in the risk for MA self-administration and how this risk interacts with MA effects on immune function. Data and samples are shared and compared across components. Thus, the MARC addresses clinically relevant themes using integrated, innovative, multidisciplinary, and translational approaches.